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用于激活沉默链霉菌生物合成基因簇的CRISPR-Cas9策略。

CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters.

作者信息

Zhang Mingzi M, Wong Fong Tian, Wang Yajie, Luo Shangwen, Lim Yee Hwee, Heng Elena, Yeo Wan Lin, Cobb Ryan E, Enghiad Behnam, Ang Ee Lui, Zhao Huimin

机构信息

Metabolic Engineering Research Laboratory, Science and Engineering Institutes, Agency for Science, Technology, and Research (A*STAR), Singapore.

Molecular Engineering Lab, Biomedical Science Institutes, A*STAR, Singapore.

出版信息

Nat Chem Biol. 2017 Apr 10. doi: 10.1038/nchembio.2341.

Abstract

Here we report an efficient CRISPR-Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover new compounds with interesting bioactivities.

摘要

在此,我们报告了一种高效的CRISPR-Cas9敲入策略,用于激活链霉菌中沉默的生物合成基因簇(BGCs)。我们应用这一单步策略激活了五个链霉菌物种中不同类别的多个BGCs,并引发了独特代谢产物的产生,包括绿色产色链霉菌中一种新型的五角形II型聚酮化合物。这种具有潜在可扩展性的策略补充了现有的激活方法,并有助于发现具有有趣生物活性的新化合物的研究工作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d82c/5634907/b73e5422c145/nihms843849f1.jpg

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